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Monia Cito, Silvia Pellegrini, Lorenzo Piemonti and Valeria Sordi

The experience in the field of islet transplantation shows that it is possible to replace β cells in a patient with type 1 diabetes (T1D), but this cell therapy is limited by the scarcity of organ donors and by the danger associated to the immunosuppressive drugs. Stem cell therapy is becoming a concrete opportunity to treat various diseases. In particular, for a disease like T1D, caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure. New and infinite sources of β cells are strongly required. In this review, we make an overview of the most promising and advanced β cell production strategies. Particular hope is placed in pluripotent stem cells (PSC), both embryonic (ESC) and induced pluripotent stem cells (iPSC). The first phase 1/2 clinical trials with ESC-derived pancreatic progenitor cells are ongoing in the United States and Canada, but a successful strategy for the use of PSC in patients with diabetes has still to overcome several important hurdles. Another promising strategy of generation of new β cells is the transdifferentiation of adult cells, both intra-pancreatic, such as alpha, exocrine and ductal cells or extra-pancreatic, in particular liver cells. Finally, new advances in gene editing technologies have given impetus to research on the production of human organs in chimeric animals and on in situ reprogramming of adult cells through in vivo target gene activation.